Liver injury in COVID-19: an insight into pathobiology and roles of risk factors.

COVID-19 is a complex disease that can lead to fatal respiratory failure with extrapulmonary complications, either as a direct result of viral invasion in multiple organs or secondary to oxygen supply shortage. Liver is susceptible to many viral pathogens, and due to its versatile functions in the body, it is of great interest to determine how hepatocytes may interact with SARS-CoV-2 in COVID-19 patients. Liver injury is a major cause of death, and SARS-CoV-2 is suspected to contribute significantly to hepatopathy. Owing to the lack of knowledge in this field, further research is required to address these ambiguities. Therefore, we aimed to provide a comprehensive insight into host-virus interactions, underlying mechanisms, and associated risk factors by collecting results from epidemiological analyses and relevant laboratory experiments. Backed by an avalanche of recent studies, our findings support that liver injury is a sequela of severe COVID-19, and certain pre-existing liver conditions can also intensify the morbidity of SARS-CoV-2 infection in synergy. Notably, age, sex, lifestyle, dietary habits, coinfection, and particular drug regimens play a decisive role in the final outcome and prognosis as well. Taken together, our goal was to unravel these complexities concerning the development of novel diagnostic, prophylactic, and therapeutic approaches with a focus on prioritizing high-risk groups.

Sub-Flap Use of Nano-Selenium Oxide Solution Enhances Skin Flap Viability in Rats: Study the Novel Role of mTOR and p-mTOR Expression.

BACKGROUND: Nano-selenium oxide (NSeO) particles are highly noticeable due to their tissue-protective and antioxidant properties. For this purpose, the effect of NSeO was evaluated on skin flap survival and flap oxidative stress markers in rats. Also, another effect of NSeO was investigated on the expression of mTOR and p-mTOR. MATERIALS AND METHODS: Fifty rats were divided into five groups of ten. Skin flap size was 3×8 cm in all groups. Groups were: (1) Sham, (2) Flap Surgery group, (3) Flap Surgery + NSeO, (4) Flap Surgery + Rapamycin (mTOR inhibitor), (5) Flap Surgery + Rapamycin + NSeO. The flap necrosis rate was computed using the paper pattern method on day seven after surgery. After day seven, flap tissues were collected for histological evaluations. Then, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Furthermore, the expression levels of mTOR and p-mTOR were measured using the Western blot method. RESULTS: Treatment with NSeO significantly reduced necrosis (P<0.05). It also resulted in a decrease in MDA level (P<0.05). Histologically, NSeO reduced inflammation and increased positive signs of tissue healing (epithelialization, neovascularization, fibroblast migration, and granulation tissue). NSeO increased SOD activity significantly (P<0.05), whereas, using rapamycin reversed these effects. Also, in all groups, mTOR changes were not significant. Additionally, p-mTOR expression was significantly reduced in groups that rapamycin was injected. CONCLUSION: NSeO can reduce flap necrosis and enhance tissue healing in rats. So, it can potentially be used clinically to promote tissue repair significantly, and its effects are independent of the mTOR pathway. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

miRNAs; a novel strategy for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is the seventh member of the bat severe acute respiratory syndrome family. COVID-19 can fuse their envelopes with the host cell membranes and deliver their genetic material. COVID-19 attacks the respiratory system and stimulates the host inflammatory responses, enhances the recruitment of immune cells, and promotes angiotensin-converting enzyme 2 activities. Patients with confirmed COVID-19 may have experienced fever, dry cough, headache, dyspnea, acute kidney injury, acute respiratory distress syndrome, and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. However, these approaches may not be good treatment options. Therefore, the search for an alternative-novel therapy is urgently important to prevent the disease progression. Recently, microRNAs (miRNAs) have emerged as a promising strategy for COVID-19. The design of oligonucleotide against the genetic material of COVID-19 might suppress virus RNA translation. Several previous studies have shown that host miRNAs play an antiviral role and improve the treatment of patients with COVID-19. miRNAs by binding to the 3'-untranslated region (UTR) or 5'-UTR of viral RNA play an important role in COVID-19-host interplay and viral replication. miRNAs interact with multiple pathways and reduce inflammatory biomarkers, thrombi formation, and tissue damage to accelerate the patient outcome. The information in this review provides a summary of the current clinical application of miRNAs for the treatments of patients with COVID-19.

The critical role of mesenchymal stromal/stem cell therapy in COVID-19 patients: An updated review.

New coronavirus disease 2019 (COVID-19), as a pandemic disaster, has drawn the attention of researchers in various fields to discover suitable therapeutic approaches for the management of COVID-19 patients. Currently, there are many worries about the rapid spread of COVID-19; there is no approved treatment for this infectious disease, despite many efforts to develop therapeutic procedures for COVID-19. Emerging evidence shows that mesenchymal stromal/stem cell (MSC) therapy can be a suitable option for the management of COVID-19. These cells have many biological features (including the potential of differentiation, high safety and effectiveness, secretion of trophic factors and immunoregulatory features) that make them suitable for the treatment of various diseases. However, some studies have questioned the positive role of MSC therapy in the treatment of COVID-19. Accordingly, in this paper, we will focus on the therapeutic impacts of MSCs and their critical role in cytokine storm of COVID-19 patients.

A qualitative exploration of the factors associated with initiation to methamphetamine use in Iran.

BACKGROUND: Crystal (methamphetamine) is a strong stimulant of addictive substances that affects the central nervous system. The consumption of this substance is increasing among teenagers and adult young people in the country. In this matter, one of the practical and important ways to its control is to identify the factors leading to its first use. Thus this paper, explores the factors related to the first crystal use in Golestan province, Iran. METHODS: In a qualitative study, 19 crystal users were recruited in the study conducted in Golestan province by snowball sampling from DIC (Drop-In Center) in addiction treatment centers. The interviews were mostly carried out individually with the participants; only one interview was conducted in an addiction treatment camp in the form of a group-focused discussion. Data analysis was implemented through content analysis in MAXQDA 10 software. RESULTS: The mean age of the participants was 35.05 ± 6.06 years with a range of 23-46 years. Meanwhile, the mean of crystal use period was 7.42 (SD: 3.61) and a range of 1-14 years. Based on the obtained data, the reasons for first crystal use could be categorized in six; 1: "crystal use to other drugs rehabilitation"; 2: "Lack of awareness of the addictive nature of crystal"; 3: "stimulating curiosity in public with crystal-use friends", 4: affordable and convenient use", 5: "anti-sleeping effects and increasing work efficiency", and 6: "therapeutic and other misconceptions"". CONCLUSIONS: The results indicated that crystal is mostly abused to opium rehabilitation. The lack of awareness and misconceptions about this substance can lead people to crystal use. Therefore, designing public health interventions to increase awareness about negative consequences of crystal use is fundamental to prevent people from abusing it. We suggest designing public health program to promote awareness about health risks of crystal and modifying related misconceptions. Finally, the government can establish policies to mandate sale tax for crystal producers and reduce easy access to crystal especially among youth.

Assessment of mechanism, type and severity of injury in multiple trauma patients: A cross sectional study of a trauma center in Iran.

PURPOSE: To accurately assess the mechanism, type and severity of injury in Iranian multiple trauma patients of a trauma center. METHODS: Patients with multiple traumas referring to the emergency department of Hasheminejad University Hospital in Mashhad, Iran, entered this cross sectional study from March 2013 to December 2013. All the patients with injury severity score (ISS) > 9 were included in this study. Data analysis was performed by SPSS software (Version 11.5) and P values less than 0.05 were considered as significant differences. RESULTS: Among the 6306 hospitalized trauma patients during this period, 148 had ISS>9. The male female ratio was 80%. The mean age of the patients was (33.5 ± 19.3) years. And 71% of the patients were younger than 44 years old. There were 19 (13%) deaths from which 68.5% were older than 44 years old. The mean transfer time from the injury scene to hospital was (55 ± 26) minutes. The most frequent mechanisms of injury were motorcycle crashes and falling from height, which together included 66.2% of all the injuries. A total of 84% of hospital deaths occurred after the first 24 h of hospitalization. Head and neck were the most common body injured areas with a prevalence of 111 cases (75%). CONCLUSION: Motorcycle crashes have high frequency in Iran. Since most victims are young males, injury prevention strategies should be considered to reduce the burden of injuries.

Vaccine-Derived Polioviruses and Children with Primary Immunodeficiency, Iran, 1995-2014.

Widespread use of oral poliovirus vaccine has led to an ≈99.9% decrease in global incidence of poliomyelitis (from ≈350,000 cases in 1988 to 74 cases in 2015) and eradication of wild-type poliovirus serotypes 2 and 3. However, patients with primary immunodeficiency might shed vaccine-derived polioviruses (VDPVs) for an extended period, which could pose a major threat to polio eradication programs. Since 1995, sixteen VDPV populations have been isolated from 14 patients with immunodeficiency in Iran. For these patients, vaccine-associated paralysis, mostly in >1 extremity, was the first manifestation of primary immunodeficiency. Seven patients with humoral immunodeficiency cleared VDPV infection more frequently than did 6 patients with combined immunodeficiencies. Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. On the basis of an association between VDPVs and immunodeficiency, we advocate screening of patients with primary immunodeficiency for shedding of polioviruses.

The Accuracy of Pain Measurement in Diagnosis of Scaphoid Bone Fractures in Patients with Magnetic Resonance Imaging: Report of 175 Cases.

INTRODUCTION: Scaphoid fracture is the most common fracture among the bones of the wrist. Plain radiography has a sensitivity of 59 to 79 percent for the diagnosis of scaphoid fracture after injury. Casting is done to avoid complications in patients with suspected fractures with normal radiography. Magnetic resonance imaging (MRI) has a sensitivity of 100% and a specificity of 99%. To avoid unnecessary casting and high costs, we decided to offer a way more efficient than radiography and less costly than MRI. MATERIAL AND METHODS: In the present study, 175 patients with suspected scaphoid fracture along with snuff box tenderness and normal radiography were enrolled in the study. On arrival, patients' pain score were determined using visual analog scale method with anatomical snuffbox tenderness and then MRI was performed on the patients' wrist and the results were recorded for patient in the check list. The data was then aggregated and analyzed. RESULTS: The result of MRI for fracture was negative for 90.9% and positive for 9.1%. The mean pain score was 7.3 in negative MRI group and 8.75 in positive MRI group, considering a significant difference. ROC curve graph showed that the sensitivity and specificity will be 87% and 57%, respectively for scores 7.5 and higher and 75% and 72%, respectively for scores 8.5 and higher. CONCLUSION: It seems that although this method, beside other criteria in the diagnosis of fractures, can be useful in future studies, it would not be helpful in fracture detection.

Micro-extraction, pre-concentration, and microfluidic-based separation of organophosphate insecticides followed by the miniaturized electrochemical detection system.

Introduction: A new analytical method based on the coupling of microextraction and microfluidics was developed and investigated for the pre-concentration, separation, and electrochemical detection of fenitrothion (FT) and parathion (PA) at the sub-ppm concentrations. Methods: In the first step, the microchip capillary electrophoresis technique was used to serve as a separation and detection system. Analytes were injected in the 40 mm long microchannel with 10 mm sidearms. Then, they were separated by applying a direct electrical field (+1800 V) between the buffer and detection reservoirs. 2-(n-morpholino)ethanesulfonic acid (MES) buffer (20 mM, pH 5) was used as a running buffer. The electrochemical detection was performed using three Pt microelectrodes with the width of working, counter, and reference electrodes (50, 250, and 250 µm, respectively) in the out-channel approach. Results: The system was devised to have the optimum detection potential equal to -1.2 V vs. pseudo-reference electrode. The dimensions of the SU-8 channel have 20 µm depth and 50 µm width. In the second step, an air-assisted liquid-liquid microextraction technique was used to extract and preconcentration of analytes from human blood plasma. Then, 1, 2 di-bromoethan was used as extractant solvent, the analytes were preconcentrated, and the sedimented solvent (50 µL) was evaporated in a 60 ˚C water bath followed by substitution of running buffer containing 10% ethanol. The optimal extraction cycles were found to be 8 with adding 1% NaCl to the aqueous phase. Analyzing time of the mentioned analytes was less than 100s, the precision range was 3.3 - 8.2 with a linear range of 0.8-100 ppm and 1.2-100 ppm for FT and PA, respectively. The extraction recoveries were about 91% and 87% for FT and PA, respectively. The detection limits for FT and PA were 240 and 360 ppb, respectively. Finally, the reliability of the method was investigated by GC-FID. Conclusion: The proposed method and device were validated and can be used as in situ and portable detection systems for detecting fenitrothion and parathion insecticides.

Buprenorphine induced opioid withdrawal syndrome relieved by adjunctive Magnesium: A clinical trial.

INTRODUCTION: Precipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO4) as an NMDA receptor antagonist on OWS. MATERIALS AND METHODS: The study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups. The control group received conventional therapies, including clonidine 0.1 mg tablet each hour, intravenous infusion of 10 mg diazepam every 30 min, and IV paracetamol (Acetaminophen) 1 g, while the intervention group received 3 g of MGSO4 in 20 min and then 10 mg/kg/h up to 2 h, in addition to the conventional treatment. The clinical opiate withdrawal scale (COWS) evaluated OWS at the start of the treatment, 30 min, and 2 h later. RESULTS: Both groups had similar demographic, opiate types, and COWS severity at the start of the intervention. COWS was lower in the intervention than the control group at 30 min (11.20 ± 2.86 and 14.65 ± 2.36, respectively, P = 0.002) and at 2 h (3.2 ± 1.61 and 11.25 ± 3.27, respectively, P < 0.001) after treatment. The intervention group received lesser doses of clonidine (0.12 ± 0.51 and 0.17 ± 0.45 mg, P = 0.003) and Diazepam (13.50 ± 5.87, 24.0 ± 6.80 mg, P = 0.001) than the control group. Serum magnesium levels raised from 1.71 ± 0.13 mmol/L to 2.73 ± 0.13 mmol/L in the intervention group. CONCLUSION: Magnesium can significantly reduce the severity of OWS. Additional studies are required to confirm these results.

Multivariate analysis of the phytochemical composition and antioxidant properties in twenty-five accessions across three Achillea species.

This study explored the chemical composition, antioxidant activity, and total phenol content of aerial parts from 25 accessions of three Achillea species (Achillea wilhelmsii C. Koch, Achillea vermicularis Trin., and Achillea tenuifolia Lam.). The plants were collected from various natural habitats across Iran, encompassing regions such as Central, Western, Southern, Northern, Western, and Northwestern parts of the country. Subsequently, they were grown together under field conditions. The study revealed significant variation in essential oil yields among accessions of A. wilhelmsii, ranging from 0.01 to 0.107%, A. vermicularis with a range of 0.075 to 1.5%, and A. tenuifolia showing a variation of 0.1 to 2%. The study utilized Gas Chromatography-Mass Spectrometry (GC-MS) analysis, revealing 75, 49, and 75 compounds in the essential oils of A. wilhelmsii, A. tenuifolia, and A. vermicularis, respectively. Major components included camphor, 1,8-cineole, anethole, α-pinene, and phytol in A. wilhelmsii, 1,8-cineole, camphor, levo-carvone, and δ-terpinene in A. vermicularis, and ß-cubebene, elixene, ß-sesquiphellandrene, 1,8-cineole, camphor, and δ-terpinene in A. tenuifolia. The essential oil compositions of A. wilhelmsii and A. vermicularis were predominantly characterized by oxygenated monoterpenes, whereas that of A. tenuifolia was characterized by sesquiterpenes. Cluster analysis grouped accessions into three clusters, with A. tenuifolia forming a distinct group. Principal Component Analysis (PCA) triplot (62.21% of total variance) confirmed these results and provided insights into compound contributions. Furthermore, total phenolic content and antioxidant activity of the accessions of three species were assessed over 2 years. A. tenuifolia exhibited the highest levels in both categories, with statistically significant linear regression between antioxidant activity and total phenol content for A. tenuifolia and A. wilhelmsii. These findings emphasize significant phytochemical diversity within Achillea species, positioning them as promising natural sources of antioxidants. Further exploration and selection of specific accessions within each species are crucial for unlocking their medicinal potential and supporting cultivation and conservation efforts.

World addiction medicine reports: formation of the International Society of Addiction Medicine Global Expert Network (ISAM-GEN) and its global surveys.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Stevens-Johnson syndrome and COVID-19: a case report with suspected multisystem inflammatory syndrome in children (MIS-C).

Introduction and importance: Symptoms similar to diseases such as Stevens-Johnson syndrome (SJS) and multisystemic inflammatory syndrome in children (MIS-C) were reported in pediatric coronavirus infections. Case presentation: Here, we present a 4-year-old girl with coronavirus disease 2019 (COVID-19), an earlier diagnosis of SJS, and a final diagnosis of MIS-C. Clinical discussion: Unlike the negative PCR test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the positive serological test confirmed COVID-19. Conclusion: The monitoring of this case indicated that higher coronavirus infection can delay immune reaction and cause symptoms similar to SJS.

In vitro and in vivo study on antiprotozoal activity of calcium oxide (CaO) and magnesium oxide (MgO) nanoparticles on promastigote and amastigote forms of Leishmania major.

BACKGROUND: Currently, anti-leishmanial drugs have been developed. However, the available compounds have several side effects such as drug resistance and toxicity that cause some limitation for use. The development of nanoparticles (NPs) use in biological research and the proven effectiveness of CaONPs and MgONPs on bacteria and fungi, along with the lack of information about its antileishmanial effects, have motivated this study. CaO and MgONPs possess considerable antibacterial effects because of their alkalinity and active oxygen species. This study has taken into account the impacts of these two NPs on the L. major in vitro and in vivo. METHODS: To evaluate the antileishmanial activity of NPs, the cytotoxic effect of CaONPs, MgONPs, and MgOCaONPs against L. major amastigotes, promastigotes, as well as macrophages, was evaluated using counting or MTT assay. The possible apoptosis of L. major by CaONPs, MgONPs, and MgOCaONPs was evaluated via flow cytometry assay. For in vivo study, BALB/c mice were allocated to five groups and the lesions of infected mice with L. major promastigotes were treated with a 200 µg/mL concentration CaONPs, MgONPs, and MgOCaONPs, then the mice underwent a 4-week follow-up to examine the wound diameter and survival rates. RESULTS: The XRD-pattern related to CaONPs and MgONPs indicating the cubic phase and Rocksalt cubic structures. According the effects of nanoparticle on promastigotes the IC50 values of CaONPs, MgONPs, and MgOCaONPs within 72 h were 7.9 ug/mL, 10.3 ug/mL, and 8.0 ug/mL respectively. CaONPs, MgONPs, and MgOCaONPs induced apoptosis in about 7.8%, 53.57%, and 12.8% of promastigotes. All mice presented lesions. MgONPs was the most effective in reducing the size of the lesions. CONCLUSION: According to the results of the present research, MgONPs and CaONPs showed good in vitro and in vivo effects on L. major promastigotes and intracellular amastigotes especially MgONPs, and also it seems that MgONPs are applicable in Leishmania infection treatment due to their potential antileishmanial effects.

Investigation of antileishmanial activities of CaO nanoparticles on L. tropica and L. infantum parasites, in vitro.

Stibogluconate sodium and meglumine antimoniate are the main antimonials utilised as the primary treatment option for leishmaniasis. However, have a number of side effects that limit their use. Development of nanoparticles (NPs) use in biological research and remarkable antimicrobial effects and unique optical and structural properties of CaO NPs have motivated this study to evaluated the effect of different times/dilutions of CaO NPs on Leishmania tropica and Leishmania infantum. To evaluate the antileishmanial activity of CaO NPs, the cytotoxic effect of CaO NPs against L. tropica and L. infantum amastigotes, promastigotes, as well as macrophages, was evaluated using counting and MTT assay after adding different concentrations of CaO nanoparticles (800-6.25 µg/ml) to the parasite culture. The possible apoptosis by CaO NPs were evaluated via flow cytometry assay. The XRD-pattern related to CaO nanoparticles indicating the cubic phase structures. According the effects of nanoparticle on promastigotes the IC50 values of CaO nanoparticles within 72 h were 19.81 µg/ml for L. tropica and 22.57 µg/ml for L. infantum. The percentage of the normal, apoptotic, and necrotic cells was estimated to be 82.6%, 14.81%, and 2.69% for L. tropica, and 73.6%, 23.89%, and 2.58% for L. infantum, respectively. Our results showed acceptable in vitro activity level of CaO NPs against L. tropica and L. infantum promastigotes as well as intracellular amastigotes. CaO NPs were more effective against L. infantum compared to L. tropica in vitro study.

Aspirin-Exacerbated Respiratory Disease Polymorphisms; a review study.

Aspirin exacerbated respiratory disease (AERD) is a condition caused by increased bronchoconstriction in people with asthma after taking aspirin or another NSAID. Molecular analysis of the human genome has opened up new perspectives on human polymorphisms and disease. This study was conducted to identify the genetic factors that influence this disease due to its unknown genetic factors. We evaluated research studies, letters, comments, editorials, eBooks, and reviews. PubMed/MEDLINE, Web of Sciences, Cochrane Library, and Scopus were searched for information. We used the keywords polymorphisms, aspirin-exacerbated respiratory disease, asthma, allergy as search terms. This study included 38 studies. AERD complications were associated with polymorphisms in ALOX15, EP2, ADRB2, SLC6A12, CCR3, CRTH2, CysLTs, DPCR1, DPP10, FPR2, HSP70, IL8, IL1B, IL5RA, IL-13, IL17RA, ILVBL, TBXA2R, TLR3, HLA-DRB and HLA-DQ, HLA-DR7, HLA-DP. AERD was associated with heterogeneity in gene polymorphisms, making it difficult to pinpoint specific gene changes. Therefore, diagnosing and treating AERD may be facilitated by examining common variants involving the disease.

Risk Stratification of Pulmonary Thromboembolism using Brain Natriuretic Peptide and Troponin I; a Brief Report.

INTRODUCTION: Pulmonary thromboembolism (PTE) is one of the most prevalent medical disorders, with a notable annual fatality rate. This study aimed to evaluated the accuracy of serum pro-BNP and troponin I levels in PTE diagnosis. METHODS: This cross-sectional study was implemented on 267 patients with suspected PTE (sudden chest pain or sudden dyspnea) in Imam Reza Hospital in Mashhad, Iran. All patients underwent pulmonary computed tomography (CT) angiography (as the gold standard test) and their serum levels of troponin I and pro-BNP were measured. The screening performance characteristics of pro-BNP in detection of PTE cases were measured and reported using receiver operating characteristic (ROC) curve analysis. RESULTS: Two-hundred-sixty-seven patients with a mean age of 67.7 ±11.5 years were evaluated (60.1% male). PTE was confirmed via CT angiography in 121 patients. The area under the ROC curve of troponin I and pro-BNP in detection of PTE was 0.501 ng/mL and 0.972 pg/mL, respectively. The sensitivity and specificity of proBNP at the best cut-off point (100 pg/ml) were 85.4% and 80.2%, respectively. The sensitivity and specificity of troponin I at the best cut-off point (0.005 ng/ml) were 65.5% and 42%, respectively. CONCLUSION: Due to the comparatively good sensitivity and specificity of proBNP in diagnosis of pulmonary thromboembolism, it can be employed as a diagnostic determinant in patients with suspected pulmonary thromboembolism along with other laboratory tests.

Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study.

Aim: COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. Objective: to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. Methods: A virtual screening of ZINC natural products on SARS-CoV-2 nsp12's druggable cavity was performed. A lead compound with the highest affinity to nsp12 was simulated dynamically for 10 ns. Results: ZINC03977803 was nominated as the lead compound. The results showed stable interaction between ZINC03977803 and nsp12 during 10 ns. Discussion: ZINC03977803 showed stable interaction with the catalytic subunit of SARS-CoV-2, nsp12. It could inhibit the SARS-CoV-2 life cycle by direct interaction with nsp12 and inhibit RdRp complex formation.